Mouse hepatitis virus (MHV) is an ubiquitous mouse pathogen with a number of potential or real adverse effects on the research usefulness of infected mice. Much of the published work on MHV has involved artificial routes of inoculation, atypical or virulen strains, microbially undefined mice and emphasis on only a few target organs. The proposed work seeks to define the pathogenesis of MHV under conditions which simulate natural infection, in an effort to generate information which can be practically applied toward controlling, diagnosing and understanding the true potential of this agent in laboratory mice. The pathogenesis of a low virulence MHV strain (MHV-S) will be studied in genetically susceptible (Balb/c) and resistant (A/J) mice of differing ages following intranasal inoculation. At sequential intervals after infection, antibody response (immunofluorescence and neutralizing antibody, antibody-dependent complement-/ and cellular mediated-cytolysis), cell mediated (T-cell) immune response, local and systemic interferon and natural killer cell response will be compared to patterns of virus recovery, antigen and lesions. Differences in disease patterns will be compared among mice of different ages to determine conditions most likely to result in limited, fulminent or persistent infection as well as potential sites and duration of virus excretion. The role of host genotype in MHV infections limited to mucosal surfaces will be explored, using an exclusively enterotropic strain of MHV (MHV-Y). Other studies are planned to investigate the ability of MHV pre-exposure to secondary challenge with antigenically homologous or heterologous strains of MHV with similar or different organotropism. Mechanisms of natural MHV transmission by direct and indirect contact and in utero transmission at different stages of pregnancy will be examined. The mechanisms by which MHV interferes with other murine respiratory pathogens and virus infections initiated by other routes of inoculation will be explored. The implications of such interference for murine diagnostic and experimental virology are significant.